Deficits in brain nicotinic acetylcholine receptor (nAChR) expression have been reported in neurodegenerative and mental diseases. Therefore, nicotinic acetylcholine agonists are being developed to alleviate these deficits. Nicotine addiction is also being treated with nAChR agonists, including nicotine. While a variety of nicotine analogs have been synthesized and investigated using radioligand binding measurements (Wang et al., 1994; Lin et al., 1994; Lin et al., 1995; others), a comparative analysis of their functional effects (ability to activate) on alpha4beta2 and other brain nAChRs has not yet been made. Earlier studies reporting the consequence of structural modification of nicotine focused upon alpha4beta2 receptors, which display exceptionally high affinity for nicotine. While this receptor plays an important role in nicotine addiction and in cognition, another homomeric alpha7 receptor also contributes to cognitive function and also to inflammatory cell function. Nicotinic drug design for the alpha4beta2 receptors has utilized nicotine's two ring structure as a lead scaffold to synthesize new drug candidates. Since nicotine displays a relatively low affinity for alpha7 nAChRs, its structure has not been considered a promising scaffold for the design of new drugs that affect this receptor.